Tn antigen (GalNAc-a-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors. Elevated levels are correlated with cancer progression and prognosis. Tn antigen is found abnormally over-expressed in various cancers by inhibiting the further extension of glycosylation. The substrate specificity and specific molecular chaperon of T-synthase core 1 β3-Gal-T-specific molecular chaperone (Cosmc) have also been demonstrated by previous studies. Thus, either a defective T-synthase or decreased expression of Cosmc could prevent the extension of O-linked glycosylation of mucin, resulting in an apparently increased expression of Tn antigen. When further extension of O-linked glycosylation is blocked, Tn antigen can also be further modified with sialic acid residue by alpha-2,6-sialyltransferase to generate sialyl Tn (NeuAca6GalNAc-Ser/Thr, sTn). US 20030170249 and US20070275019 provide a vaccine comprising: (a) a pharmaceutically effective amount of a carbohydrate antigen found on said cancer cells, or a mimetic thereof; and (b) a pharmaceutically acceptable carrier. The carbohydrate antigen can be Tn or sialyl-Tn. US 20100278818 provides a pharmaceutical composition comprising an antibody, directed against Tn antigen. U.S. Pat. No. 8,383,767 found that coupling a glycoantigen Tn, sTn, or GM3 with a protein carrier containing an immunoglobulin (Ig) Fc domain and a cysteine-rich domain significantly improved its antigenicity. Chiang et al. developed an anti-Tn vaccine, which induces anti-Tn antibodies in mice with high specificity and high affinity using linear array epitope technology (H. L. Chiang, C. Y. Lin, F. D. Jan, Y. S. Lin, C. T. Hsu, J. Whang-Peng, L. F. Liu, S. Nieh, C. C. Lin, J. Hwang, A novel synthetic bipartite carrier protein for developing glycotope-based vaccines. Vaccine 30 (2012)7573-7581).
There are also reports that Tn is elevated in inflammatory tissues; the expression of Tn is associated with the extent of inflammatory response upon tissue damage. For example, Tn syndrome is characterized by the detection of Tn antigen on blood cells of all lineages. Tn antigen can be detected on the IgA1 hinge region in some IgA nephropathy patients. Additionally, Tn is known to express in chronic inflammatory tissues such as those from patients with rheumatoid arthritis and osteoarthritis. Elevated Tn expression has been observed in inflammation-inflicted tissue damage and found to be associated with modulation of the host immune response.
Hyperoxia increases NF-κB translocation in fetal and adult lung fibroblasts and the production of proinflammatory mediators such as tumor necrosis factor-α (TNF-α), interferon-γ, and interleukin-1β (IL-1β) (H. D. Li, Q. X. Zhang, Z. Mao, X. J. Xu, N. Y. Li, H. Zhang, Exogenous interleukin-10 attenuates hyperoxia-induced acute lung injury in mice. Exp. Physiol. 100 (2015) 331-330; and C. J. Wright, P. A. Dennery, Manipulation of gene expression by oxygen: a primer from bedside to bench. Pediatr. Res. 66 (2009) 3-10). Prolonged exposure to hyperoxia leads to inflammation and acute lung injury. No effective therapies have yet been established.